Pharmacokinetic/pharmacodynamic modeling in drug research and development

The two domains in clinical pharmacology dealing with optimizing dosing rec ommendations are pharmacokinetics and pharmacodynamics. However, the useful ness of these disciplines is limited if viewed in isolation. Pharmacokineti c/pharmacodynamic (PK/PD) relationships and modeling builds the bridge betw een these two classical disciplines of clinical pharmacology. It links the concentration-time profile as assessed by pharmacokinetics to the in tensit y of observed response as quantified by pharmacodynamics. Thus, the resulti ng so-called integrated PK/PD-models allow the description of the complete time course of the desired and/or undesired effects in response to a drug t herapy. PK/PD-modeling can elucidate the causative relationship between dru g exposure and response and provide a better understanding of the sequence of events that result in the observed drug effect. This information can the n be used to streamline the drug development process and dose optimization. This consensus paper presents an update on the current state of PK/PD-mode ling from an academic, industrial and regulatory perspective. (C)2000 the A merican College of Clinical Pharmacology.